Analysis of the ubiquitin-modified proteome identifies novel host factors in Kaposi's sarcoma herpesvirus lytic reactivation.

Unlabelled: Kaposi's sarcoma herpesvirus (KSHV) is the causative agent of Kaposi's sarcoma and is associated with primary effusion lymphoma (PEL), multicentric Castleman's disease, and two inflammatory diseases. KSHV-associated cancers are primarily associated with genes expressed during latency, while other pathologies are associated with lytic gene expression. The major lytic switch of the virus, Replication and Transcription Activator (RTA), interacts with cellular machinery to co-opt the host ubiquitin proteasome system to evade the immune response as well as activate the program of lytic replication.

Lessons Learned About Trauma Related to Racial Discrimination During COVID-19 in the United States.

Race scholars have discussed how the pandemic has disproportionately burdened marginalized communities and exacerbated pre-existing inequities, particularly for Black Indigenous People of Color (BIPOC) in the United States (U.S.).

Adjuvant Trastuzumab Emtansine Versus Paclitaxel Plus Trastuzumab for Stage I Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: 5-Year Results and Correlative Analyses From ATEMPT.

Purpose: Long-term outcomes of patients with stage I human epidermal growth factor receptor 2 (HER2)-positive breast cancer receiving adjuvant trastuzumab emtansine (T-DM1) remain undefined, and prognostic predictors represent an unmet need.

Methods: In the ATEMPT phase II trial, patients with stage I centrally confirmed HER2-positive breast cancer were randomly assigned 3:1 to adjuvant T-DM1 for 1 year or paclitaxel plus trastuzumab (TH). Coprimary objectives were to compare the incidence of clinically relevant toxicities between arms and to evaluate invasive disease-free survival (iDFS) with T-DM1.

Impact of Neoadjuvant Paclitaxel/Trastuzumab/Pertuzumab on Breast Tumor Downsizing for Patients with HER2+ Breast Cancer: Single-Arm Prospective Clinical Trial.

Background: The impact of abbreviated neoadjuvant regimens for HER2+ breast cancer on rates of breast conservation therapy (BCT) is unclear. We aimed to determine BCT rates in a single-arm prospective trial of neoadjuvant paclitaxel/trastuzumab/pertuzumab (THP) in patients with stage II or III HER2+ breast cancer.

Study Design: BCT eligibility was prospectively recorded before and after THP.

Health in Down syndrome: creating a conceptual model.

Background: Down syndrome (DS) has a unique medical and psychological profile that could impact how health is defined on three dimensions: physical, social and mental well-being.

Methods: In 2021, we presented our proposed conceptual model to three expert panels, four focus groups of parents of individuals with DS age 0-21 years and four focus groups of individuals with DS age 13-21 years through videoconferencing technology. Participants gave feedback and discussed the concept of health in DS.

Validation of bladder health scales and function indices for women's research.

Background: Existing bladder-specific measures lack the ability to assess the full range of bladder health, from poor to optimal health.

Objective: This study aimed to report evidence of validity of the self-administered, multidimensional bladder health scales and function indices for research in adult women.

Study Design: A cross-sectional population-based validation study with random assignment to paper or electronic administration was conducted using national address-based probability sampling supplemented by purposive sampling of women with lower urinary tract symptoms in 7 clinical research centers.

Proxy-report in individuals with intellectual disability: A scoping review.

Background: Views can be collected from individuals (self-report) or others on their behalf (proxy-report).

Objective: We aimed to review the literature on methods and statistical approaches used to evaluate observer versus self-report responses from individuals with intellectual disability or Down syndrome.

Methods: A series of key questions related to statistical approaches and data collection methods were formulated a priori to inform the search strategy and review process.

A prospective trial of treatment de-escalation following neoadjuvant paclitaxel/trastuzumab/pertuzumab in HER2-positive breast cancer.

De-escalating adjuvant therapy following pathologic complete response (pCR) to an abbreviated neoadjuvant regimen in human epidermal growth factor receptor 2-positive (HER2+) breast cancer is the focus of international research efforts. However, the feasibility of this approach and its appeal to patients and providers had not been formally investigated. We aimed to assess adherence to de-escalated adjuvant antibody doublet therapy (trastuzumab and pertuzumab [HP], without chemotherapy) among patients with pCR following neoadjuvant paclitaxel/HP (THP).

Cardiac outcomes of subjects on adjuvant trastuzumab emtansine vs paclitaxel in combination with trastuzumab for stage I HER2-positive breast cancer (ATEMPT) study (TBCRC033): a randomized controlled trial.

The excellent outcomes seen in patients treated with adjuvant trastuzumab emtansine (T-DM1) in the ATEMPT trial and the favorable toxicity profile associated with this agent make T-DM1 a potential therapeutic option for select patients with stage I HER2-positive breast cancer. Moreover, T-DM1 is an established adjuvant treatment for patients with HER2-positive breast cancer with the residual invasive disease after neoadjuvant therapy. Given that cardiotoxicity is the most significant adverse event of trastuzumab, which is a main molecular component of T-DM1, we conducted a sub-analysis of the ATEMPT trial to determine the cardiac safety of adjuvant T-DM1.

Prospective Study Testing a Simplified Paclitaxel Premedication Regimen in Patients with Early Breast Cancer.

Background: In early trials, hypersensitivity reactions (HSRs) to paclitaxel were common, thus prompting the administration of antihistamines and corticosteroids before every paclitaxel dose. We tested the safety of omitting corticosteroids after cycle 2 during the paclitaxel portion of the dose-dense (DD) doxorubicin-cyclophosphamide (AC)-paclitaxel regimen.

Patients, Materials, And Methods: In this prospective, single-arm study, patients who completed four cycles of DD-AC for stage I-III breast cancer received paclitaxel 175 mg/m every 2 weeks for four cycles.

The Inflection Point Model: A Model to Explore the Hidden Burdens of Non-Cancerous Genitourinary Conditions.

Objective: To propose a conceptual model to identify points along the condition course where actions or inaction affect downstream burdens of non-cancerous genitourinary conditions (NCGUC).

Materials And Methods: The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) convened an interdisciplinary meeting to comprehensively consider the burdens of NCGUCs. Subsequently, the authors met monthly to conceptualize the model.

Using charcoal, ATR FTIR and chemometrics to model the intensity of pyrolysis: Exploratory steps towards characterising fire events.

This study describes a multivariate statistical model (derived using partial least squares regression, PLS-R) that derives charring intensity (reaction temperature and duration) from the attenuated total reflectance (ATR) Fourier Transform Infrared (FTIR) spectra of charcoal. Data for the model was obtained from a library of charcoal samples produced under laboratory conditions at charring intensities (CI) relevant to wildfires and a series of feedstocks representing common tree species collected from Australia. The PLS-R model developed reveals the potential of FTIR to determine the charring intensity of charcoal.

Adjuvant Trastuzumab Emtansine Versus Paclitaxel in Combination With Trastuzumab for Stage I HER2-Positive Breast Cancer (ATEMPT): A Randomized Clinical Trial.

Purpose: The ATEMPT trial was designed to determine if treatment with trastuzumab emtansine (T-DM1) caused less toxicity than paclitaxel plus trastuzumab (TH) and yielded clinically acceptable invasive disease-free survival (iDFS) among patients with stage I human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC).

Methods: Patients with stage I centrally confirmed HER2+ BC were randomly assigned 3:1 to T-DM1 or TH and received T-DM1 3.6 mg/kg IV every 3 weeks for 17 cycles or T 80 mg/m IV with H once every week × 12 weeks (4 mg/kg load →2 mg/kg), followed by H × 39 weeks (6 mg/kg once every 3 weeks).

Rationale and design of the validation of bladder health instrument for evaluation in women (VIEW) protocol.

Background: Bladder health is an understudied state and difficult to measure due to lack of valid and reliable instruments. While condition specific questionnaires assess presence, severity and degree of bother from lower urinary tract symptoms, the absence of symptoms is insufficient to assume bladder health. This study describes the methodology used to validate a novel bladder health instrument to measure the spectrum of bladder health from very healthy to very unhealthy in population based and clinical research.

Measuring Bladder Health: Development and Cognitive Evaluation of Items for a Novel Bladder Health Instrument.

Purpose: We describe the item development and cognitive evaluation process used in creating the Prevention of Lower Urinary Tract Symptoms Bladder Health Instrument (PLUS-BHI).

Materials And Methods: Questions assessing bladder health were developed using reviews of published items, expert opinion, and focus groups' transcript review. Candidate items were tested through cognitive interviews with community-dwelling women and an online panel survey.

Effect of High-Dose vs Standard-Dose Vitamin D Supplementation on Body Composition among Patients with Advanced or Metastatic Colorectal Cancer: A Randomized Trial.

Skeletal muscle and adipose tissue express the vitamin D receptor and may be a mechanism through which vitamin D supplementation slows cancer progression and reduces cancer death. In this exploratory analysis of a double-blind, multicenter, randomized phase II clinical trial, 105 patients with advanced or metastatic colorectal cancer who were receiving chemotherapy were randomized to either high-dose vitamin D (4000 IU) or standard-dose (400 IU) vitamin D. Body composition was measured with abdominal computed tomography at enrollment (baseline) and after cycle 8 of chemotherapy (16 weeks).

A dynamic portrait of adverse events for breast cancer patients: results from a phase II clinical trial of eribulin in advanced HER2-negative breast cancer.

Purpose: Adverse events (AE) during oncology clinical trials are typically reported using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), which provides information about the frequency and severity of AEs from the provider's perspective. Instruments that track patient-reported outcomes (PRO) complement the CTCAE and provide additional patient-centered information about the toxicity profile of an anti-cancer drug.

Methods: We conducted a single-arm, open-label phase II study of eribulin as first- or second-line therapy for metastatic hormone receptor-positive/HER2-negative (HR+/HER2-) or triple-negative breast cancer (TNBC).

Avoiding Peg-Filgrastim Prophylaxis During the Paclitaxel Portion of the Dose-Dense Doxorubicin-Cyclophosphamide and Paclitaxel Regimen: A Prospective Study.

Purpose: The use of growth factors adds considerable expense and some toxicity to adjuvant breast cancer chemotherapy. We tested the feasibility and safety of omitting routine peg-filgrastim use during the paclitaxel portion of the dose-dense doxorubicin-cyclophosphamide-paclitaxel regimen.

Patients And Methods: This was a prospective, single-arm study in which patients 18 to 65 years of age who completed 4 cycles of dose-dense doxorubicin-cyclophosphamide for stage I-III breast cancer received paclitaxel 175 mg/m every 2 weeks.

Phase I/II trial of the CXCR4 inhibitor plerixafor in combination with bortezomib as a chemosensitization strategy in relapsed/refractory multiple myeloma.

We tested the hypothesis that using CXCR4 inhibition to target the interaction between the tumor cells and the microenvironment leads to sensitization of the tumor cells to apoptosis. Eligibility criteria included multiple myeloma (MM) patients with 1-5 prior lines of therapy. The purposes of the phase I study were to evaluate the safety and maximal-tolerated dose (MTD) of the combination.

Evaluation of the adverse events following immunization surveillance system in Guruve district, Mashonaland Central 2017.

Introduction: An adverse event following immunisation is any untoward medical occurrence which follows vaccination. Frequency of adverse events ranges from 13% to 34% and they should be reported regardless of severity. From the beginning of 2016 to mid-2017, Guruve district in Zimbabwe did not report any AEFIs.